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Quantification of miRNA-mRNA Interactions 英文参考文献
QuantificationofmiRNA-mRNAInteractions
AnderMuniategui1,Rube′nNogales-Cadenas2,Migue′lVa′zquez3,XabierL.Aranguren4,XabierAgirre5,
AernoutLuttun4,FelipeProsper5,AlbertoPascual-Montano2,AngelRubio1*
1GroupofBioinformatics,CEITandTECNUN,UniversityofNavarra,SanSebastian,Spain,2NationalCenterforBiotechnology-CSIC,Madrid,Spain,3StructuralBiologyand
BiocomputingProgramme,SpanishNationalCancerResearchCentre(CNIO),Madrid,Spain,4CenterforMolecularandVascularBiology,KatholiekeUniversiteitLeuven,
Leuven,Belgium,5HematologyDepartmentandAreaofCellTherapy,Cl?′nicaUniversidaddeNavarra,FoundationforAppliedMedicalResearch,UniversityofNavarra,
Pamplona,Spain
Abstract
miRNAsaresmallRNAmolecules(922nt)thatinteractwiththeircorrespondingtargetmRNAsinhibitingthetranslationof
themRNAintoproteinsandcleavingthetargetmRNA.Thissecondeffectdiminishestheoverallexpressionofthetarget
mRNA. Several miRNA-mRNA relationship databases have been deployed, most of them based on sequence
complementarities.However,thenumberoffalsepositivesinthesedatabasesislargeandtheydonotoverlapcompletely.
Recently, it has beenproposed to combineexpression measurement fromboth miRNA andmRNA andsequence based
predictionstoachievemoreaccuraterelationships.Inourwork,weuseLASSOregressionwithnon-positiveconstraintsto
integrate both sources of information. LASSO enforces the sparseness of the solution and the non-positive constraints
restrictthesearchofmiRNAtargetstothosewithdown-regulationeffectsonthemRNAexpression.Wenamedthismethod
TaLasso(miRNA-TargetLASSO).
WeusedTaLassoontwopublicdatasetsthathavepairedexpressionlevelsofhumanmiRNAsandmRNAs.Thetopranked
interactionsrecoveredbyTaLassoareespeciallyenriched(morethanusinganyotheralgorithm)inexperimentallyvalidated
targets.ThefunctionsofthegeneswithmRNAtranscriptsinthetop-rankedinteractionsaremeaningful.Thisisnotthecase
usingotheralgorithms.
TaLassoisavailableasMatlaborRcode.Thereisalsoaweb-basedtoolforhumanmiRNAsatb.csic.es/.
Citation: Muniategui A, Nogales-Cadenas R, Va′z
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